Engineered Platform for Immune Isolation and Modulation in Pancreatic Islet Transplantation For Type-1 Diabetes

Islet microencapsulation through permselective hydrogels may improve safety and efficacy of transplantation, maintain immunoisolation, and offer metabolic control without chronic and systemic immunosuppression. Impaired transport of glucose/insulin and/or inflammatory responses by the host immune system to the capsules may decrease encapsulated islet functionality. I engineered a platform for immune isolation and modulation of pancreatic islets combining microencapsulation with targeted delivery of immunomodulatory drugs to increase their functionality after transplantation. I performed parallel evaluations of alginate single and double capsules (SC, DC) versus polyethylene glycol (PEG) conformal coating (CC) of human islets. With data obtained in silico and in vivo, I concluded that minimal capsule size is critical for metabolic control and improving the biocompatibility of CC grafts in the site of transplantation using localized and targeted immunomodulation may be beneficial to increase the efficacy of CC grafts. To improve CC biocompatibility, I tested anti-inflammatory dexamethasone (Dex) and cyclosporine A (CsA) loading efficiency and release kinetics in Drug-Integrating Amphiphilic Nanoassemblies (DIANA) and efficacy in decreasing inflammatory cytokine secretion by activated macrophages while maintaining islet functionality in vitro and in vivo. DIANAs loaded Dex increased water solubility by ~15 times and released it within 8 hours. nFIB localize in the site of inflammation when added locally, and nMIC target the graft after IV injection. Local and IV Dex- and CsA-DIANAs decreased inflammation three days post transplantation of CC grafts in mice. This approach can be applied to islet transplantation for improving CC biocompatibility providing optimal metabolic control without chronic systemic immunosuppression.</p

Age and Growth of Atlantic Blue Marlin (Makaira nigricans) Larvae from the Coastal Waters of Cuba

Atlantic blue marlin (Makaira nigricans) are the largest species among the Istiophorids in the Atlantic Ocean with primary spawning grounds in the northern Caribbean and Bahamas. We examined the early life history dynamics of blue marlin relating to growth, distribution, and habitat conditions. Although larval growth has been described from adjacent areas in the Atlantic, this study sourced larvae from Cuba, one of the hotspots of the distribution of the species. Blue marlin larvae were collected in 2015 and 2016, were genetically identified, and 157 sagittal otoliths were aged. Larval growth rates (mm day-1) are reported for the first two weeks by examining the number of daily increments and relating these to the standard larval length (mm). Although linear and exponential models were used to estimate the rate of growth between years (2015 & 2016) and regions (north and south), the exponential growth model was a better fit. The instantaneous growth rates for samples collected in Cuba were very similar (North 2015: 0.099; South 2015: 0.124; North 2016: 0.116). However, larvae collected in the North of Cuba were larger at age than the South, yet their instantaneous growth rates were very similar, and no statistical differences in growth rates were detected between these two regions. When examining environmental conditions between regions (North & South) chlorophyll differed and between years (2015 & 2016) salinity differed. Understanding larval distribution and larval growth variability can influence blue marlin recruitment and may be related to environmental conditions in the Atlantic Basin

Cancer Progression in Retinoblastoma: Chemoresistance and BCOR

Retinoblastoma is the most common pediatric eye cancer with 8000 new diagnoses worldwide each year. Although treatment strategies have significantly improved over the past few decades, severe post-treatment ocular complications and limited pharmacological options as secondary treatment emphasize the need for therapeutic discovery. The most significant barrier to this is our gap in knowledge regarding mechanisms underlying retinoblastoma cancer progression. Our objective is to shed insight into two major contributors to tumor progression: chemoresistance and BCOR loss. Here, we demonstrate repeated sublethal exposure of retinoblastoma to the widely used chemotherapy agent carboplatin results in generalized induction of transcriptomic reprogramming involving the PI3K-AKT pathway, ABC transporters, and metabolic regulators. We also propose a multi-faceted role for BCOR in retinoblastoma involving cell cycle and hypoxia. Altogether, these investigations provide a deeper understanding of mechanisms underlying retinoblastoma cancer progression and serve as a stepping-stone for downstream therapeutic discovery to improve patient care.</p

A Pedagogical Approach to Woodwind Doubling Through Contrasting Examples From Musicals

Woodwind doubling, or the practice of performing on two or more woodwind instruments from different instrumental families, has become increasingly popular in recent years.&nbsp; This essay analyzes three musical examples to find what skills are necessary to successfully perform as a professional woodwind doubler. The selected excerpts come from the musical "West Side Story" (comp. Leonard Bernstein, 1957), the musical "Sunday in the Park with George" (comp. Stephen Sondheim, 1984), and the musical film "Shall We Dance" (comp. George Gershwin, 1937), and each excerpt highlights specific challenges that a woodwind doubler may face. Currently, there are few methods available to help prepare the woodwind performer for woodwind doubling performance situations. Composing a new set of etudes to address specific problem areas in woodwind doubling will provide an opportunity to expand the materials available to improve wooding doubling skills. These etudes are based on musical examples found in woodwind doubling situations and allow musicians to see what is typically asked in these situations.</p

50 - Cardiac Arrest and Life-Threatening Arrhythmias

Sudden cardiac arrest, as the mechanism for unexpected deaths, accounts for 50% of all cardiovascular deaths and is the first clinically recognized cardiovascular event in 50% of these victims. Electrical mechanisms of sudden cardiac arrest are shockable rhythms, including ventricular fibrillation (VF) and pulseless ventricular tachycardia (pulseless VT), and nonshockable rhythms, such as pulseless electrical activity and asystole. Shockable rhythms provide a better opportunity for return of spontaneous circulation and survival. The most common causes of cardiac arrest are consequences of coronary artery disease, such as acute ischemia and ischemic cardiomyopathy. The various nonischemic cardiomyopathies, and other acquired or inherited disorders, account for a smaller proportion of the events. Survival from sudden cardiac arrest free of neurologic dysfunction is dependent upon a rapid return of spontaneous circulation. Cardiopulmonary resuscitation (CPR) initiated by bystanders immediately after summoning emergency rescue and rapid defibrillation with community-based automated defibrillators improve survival. Advanced life support includes activities—such as intubation, administration of antiarrhythmic drugs, and other therapies—that may restore circulation when return of spontaneous circulation is not immediate. An important consequence of sudden cardiac arrest is brain damage, due to ischemic encephalopathy and resulting coma. Among out-of-hospital cardiac arrest victims who are resuscitated and hospitalized, brain damage is the most important cause of subsequent in-hospital death and long-term disabilities. Outcomes can be improved by preventing hyperthermia in the comatose cardiac arrest victim. Among those whose sudden cardiac arrest is not secondary to reversible causes, implantable cardioverter-defibrillators provide long-term protection against death from recurrent sudden cardiac arrest

Chemosensory function recovery in COVID-19 patients: A cross-sectional study

To determine whether subjects who have recovered from COVID-19 smell and taste disturbance perform similarly to their COVID-naïve baseline, on gold-standard smell and taste tests. Prospective cross-sectional study. University of Miami Department of Otolaryngology in Miami, FL between September 2021, and August 2022. Those previously COVID-19 positive composed the experimental group, those who reported being COVID-naïve composed the control group. Mean total score for the UPSIT Smell Test, and the Burghart Taste Strip test were the primary outcome measures. 70 adult subjects (35 former COVID-positive, 35 COVID-naïve) were enrolled, with 21 females and 14 males in each group. 87 % of all subjects were white and were almost distributed evenly between Hispanic and non-Hispanic. Mean UPSIT total score for the experimental group was 30.6 (95 % CI 28.9–32.3), mean UPSIT total score for the control group was 31.2 (95 % CI 29.7–32.8). Mean Burghart total score for the experimental group was 11.3 (95 % CI 10.6–12.0), mean Burghart total score for the control group was 10.7 (95 % CI 9.7–11.8). These showed a significant overlap of the 95 % CI of the mean total score between the control group and the experimental group, suggesting no significant difference between the two groups. These results suggest that COVID-19 patients who experience smell and taste disturbance and recover, regain sensory ability similar to their pre-COVID ability. Further study is needed to validate these findings, but the results are promising in the long-term recovery of COVID-19

158 - Pelvic fractures and long bone fractures

Pelvic and long bone fractures are common injuries, especially in blunt trauma patients, that can lead to significant morbidity and mortality. The most common manifestation of these fractures is hemorrhage, which requires “damage control resuscitation” with early blood product administration, ideally in a 1:1:1 ratio of plasma, platelets, and packed red cells. In pelvic fractures, hemorrhage requires multidisciplinary management, with adjuncts including pelvic binding, extraperitoneal pelvic packing, angioembolization, and external fixation all playing important roles in management. For long bone fractures, hemorrhage mandates assessment for vascular injury with repair or shunting as indicated, in addition to early reduction and stabilization of fractures. Global management includes antibiotic prophylaxis in open fractures, initiation of early enteral nutrition, use of prophylactic heparinoids because of the high risk of venous thromboembolism, and the rare case of fat embolism syndrome requiring supportive respiratory care. Specific considerations include simultaneous urinary tract and/or rectal injury in pelvic fractures and compartment syndrome and/or rhabdomyolysis in lower extremity fractures, all of which occur infrequently but can have devastating consequences if unrecognized and require a high index of clinical suspicion

The Unintended Consequences of National Legal Institutions on Firms’ Strategic Decisions

This dissertation examines the unintended consequences of national legal institutions on firms&rsquo; strategic decisions and consists of three empirical essays. Findings from the first essay indicate that firms with high domestic market dependence and located in countries with weak institutional development (closed economies) increase R&D investment when protected by the passage of national security screening laws. Findings from the second essay indicate that the presence of leniency laws, intended to improve consumer welfare by increasing competition can instead harm consumers by increasing firms&rsquo; product irresponsibility events. Findings from the third essay suggest that the existence of global board reforms which hold boards more accountable can instead increase employee accidents when shareholders accumulate power and demand stronger firm performance. This dissertation can contribute to research by highlighting the salience of national legal institutions and how they shape firms&rsquo; strategic decisions and can affect their product responsibility and workplace safety outcomes.</p